1. The GUDMAP Database: An Online Resource for Genitourinary Research Dr. Simon Harding Stem Cells & Bioinformatics 22 nd September 2009

2. Overview GUDMAP: Introduction The Data In Situ, Microarray and statistics The Website Basic features – browsing and querying Additional tools – gene expression summaries, disease resource Examples of Use Complex Boolean anatomy query kidney Reproductive system

3. GUDMAP: Introduction GenitoUrinary Development Molecular Anatomy Project Goal: Provide the scientific research community with tools to facilitate research through a molecular atlas of gene expression in developing organs of mouse GU system Worldwide consortium based project USA Australia UK – Edinburgh Funded by NIH, NIDDK

4. GUDMAP: Introduction Why GUDMAP? Community resource to enhance existing research and stimulate new research High resolution molecular anatomy of the developing GU system Markers for anatomically defined cell types Describe developmental processes that establish function domains Understand genesis of organ anatomy at molecular/cellular level New level of understanding to benefits treatment of disorders and disease of GU system GUDMAP Edinburgh Human Genetics Unit & University of Edinburgh Curating data and making it accessible through a website Raw data available to research community Easy-to-use window onto this data – web-interface

5. GUDMAP: In Situ Data In situ data In situ hydbridisation (section & wholemount) Immunohistochemistry (section) In situ analysis of transgenic reporter screens (wholemount) GUDMAP:11296GUDMAP:7156

6. GUDMAP: Microarray Data Microarray data Array analysis of laser-captured components of developing GU system - enrichment Array analysis of FACS-isolated cells from transgenic reporter mice - purification

7. GUDMAP: Statistics ISHMAIHCTg GenesEntriesGenesEntriesGenesEntriesGenesEntries Metanephros 27855449-1297916 Lower Urinary System 26894902-540016 Early Reproductive System 227253-110000 Male Reproductive System 23642831-332213 Female Reproductive System 22922741-151113 Total 29077728-25991216

8. GUDMAP: The Website BROWSE Microarrays, in situs, by stage, genes QUERY gene anatomy function boolean anatomy FOCUS Focus query to distinct anatomical groups

9. Search result GUDMAP Entry Details

10. Annotation in a GUDMAP entry Annotation Notes High resolution ontology Signal is strongest on the side of the vesicle furthest from the ureteric tip

11. Select components from tree Adjust parameters Syntax allows for more advanced queries

13. GUDMAP: Gene strip Summarising gene expression Gene Page Disease Associations Disease Associations In situ expression entries In situ expression entries In situ image matrix In situ image matrix Microarray expression Microarray expression

14. GUDMAP: Linking to disease Why? Link between gene expression, GU development and GU disease Studying gene expression in the genitourinary (GU) system is useful to understand GU disease. If we know that a particular disease affects the GU system we can look at which genes are expressed (or not expressed) in the affected GU tissues and structures. Help to better understand aetiology of disease. Some diseases occur as a consequence of events taking place during development, e.g. incorrect formation of structures.

15. Disease Resource Associations between genes and OMIM disease Associations between genes and mammalian renal/urinary/reproductive phenotypes (MGI) Disease-gene associations are searchable with results presented in a simple table. GUDMAP: Linking to disease OMIM:Online Mendelian Inheritance in Man (www.ncbi.nlm.nih.gov/sites/entrez?db=OMIM) NCBI:National Center for Biotechnology Information (www.ncbi.nlm.nih.gov/) MGI:Mouse Genome Informatics (www.informatics.jax.org)

16. What genes specifically mark the structure I am interested in examining? Ureteric Tip Looking for gene expressed in ureteric tip but not in surrounding structures Strategy - use Boolean Anatomy Query GUDMAP: Example

17. What genes specifically mark the structure I am interested in examining?

18. Boolean Query syntax – to build complex query Save larger queries to a file or in collections Query for ureteric tip at TS23 (E15.5) GENE: nd{in cap mesenchyme TS23..TS23} AND | nd{in early tubule TS23..TS23} AND | nd{in late tubule TS23..TS23} AND | nd{in renal vasculature TS23..TS23} AND | nd{in ureter TS23..TS23} AND | p{in ureteric tip TS23..TS23} AND | nd{in ureteric trunk TS23..TS23} AND | nd{in renal interstitium group TS23..TS23} What genes specifically mark the structure I am interested in examining?

21. University of Edinburgh & MRC Human Genetics Unit GUDMAP Editorial Office Duncan Davidson Jamie Davies Jane Armstrong Jane Brennan Sue Lloyd-MacGilp Chris Armit GUDMAP Database Development Team Derek Houghton Mehran Sharghi Xingjun Pi Ying Cheng Koosum Roochun Harvard University Andy McMahon et al University of Queensland Melissa Little et al Peter Koopman et al Sean Grimmond et al Cincinnati Children's Hospital Medical Center Bruce Aronow et al Steve Potter et al Jim Lessard et al Columbia University Cathy Mendelsohn et al Vanderbilt University Michelle Southard-Smith et al Research Triangle, NC Kevin Gaido et al Acknowledgements